EB病毒编码的癌蛋白LMP1通过ERK-MAPK依赖机制招募并转化成纤维细胞。

The EBV-Encoded Oncoprotein, LMP1, Recruits and Transforms Fibroblasts via an ERK-MAPK-Dependent Mechanism.

作者信息

Davis Alexandra M, Rapley Abigail, Dawson Christopher W, Young Lawrence S, Morris Mhairi A

机构信息

Faculty of Health and Life Sciences, De Montfort University, Leicester LE1 9BH, UK.

Warwick Medical School, University of Warwick, Coventry CV4 8UW, UK.

出版信息

Pathogens. 2021 Aug 3;10(8):982. doi: 10.3390/pathogens10080982.

DOI:10.3390/pathogens10080982

PMID:34451446

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8400670/

Abstract

Latent membrane protein 1 (LMP1), the major oncoprotein encoded by Epstein-Barr virus (EBV), is expressed at widely variable levels in undifferentiated nasopharyngeal carcinoma (NPC) biopsies, fueling intense debate in the field as to the importance of this oncogenic protein in disease pathogenesis. LMP1-positive NPCs are reportedly more aggressive, and in a similar vein, the presence of cancer-associated fibroblasts (CAFs) surrounding "nests" of tumour cells in NPC serve as indicators of poor prognosis. However, there is currently no evidence linking LMP1 expression and the presence of CAFs in NPC. In this study, we demonstrate the ability of LMP1 to recruit fibroblasts in vitro in an ERK-MAPK-dependent mechanism, along with enhanced viability, invasiveness and transformation to a myofibroblast-like phenotype. Taken together, these findings support a putative role for LMP1 in recruiting CAFs to the tumour microenvironment in NPC, ultimately contributing to metastatic disease.

摘要

潜伏膜蛋白1（LMP1）是由爱泼斯坦-巴尔病毒（EBV）编码的主要癌蛋白，在未分化鼻咽癌（NPC）活检组织中的表达水平差异很大，这引发了该领域对于这种致癌蛋白在疾病发病机制中的重要性的激烈争论。据报道，LMP1阳性的鼻咽癌更具侵袭性，同样，鼻咽癌中肿瘤细胞“巢”周围存在癌症相关成纤维细胞（CAF）是预后不良的指标。然而，目前尚无证据表明NPC中LMP1表达与CAF的存在有关。在本研究中，我们证明了LMP1能够通过ERK-MAPK依赖性机制在体外募集成纤维细胞，同时增强其活力、侵袭性并使其转变为肌成纤维细胞样表型。综上所述，这些发现支持LMP1在将CAF募集到NPC肿瘤微环境中发挥推定作用，最终导致转移性疾病。